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Biomedical subjects

A Johns

Publications and source records attributed to A Johns.

At least 73 records · Page 4Linked to original sources
PubMed1989

Etiology, prognosis, and hemostatic function after cerebral infarction in young adults.

We retrospectively evaluated 66 patients younger than 40 years of age who presented with acute nonhemorrhagic cerebral infarction (n = 63) or transient ischemic attacks (n = 3) to determine the possible etiology and long-term outcome at a mean follow-up interval of 3 years after initial presentation. A probable cause for the stroke was identified in 24 patients (36%); this group included one woman with a history of recurrent spontaneous abortions and a positive test for the presence of the lupus anticoagulant. We performed detailed hemostatic investigations at follow-up in 38 (90%) of the remaining 42 patients in whom the cause of the stroke was unknown or uncertain; results of the basic hemostatic screening tests (including that for fibrinogen) were uniformly normal. All 38 patients demonstrated a normal fibrinolytic response as measured by tissue plasminogen activator release to a standard venous occlusion stress test; concentration of the inhibitor of tissue plasminogen activator was not increased. No abnormalities in the concentrations of the inhibitory proteins C or S or antithrombin III were identified, and none of the 38 patients had evidence of a lupus anticoagulant. Neurologic recovery was complete or the residual disability mild in 46 of 59 (78%) patients. Overall prognosis was excellent and independent of whether a precipitating factor for the stroke could be identified.

Acute Disease↗
PubMed1989

Phorbol dibutyrate inhibits release and action of endothelium-derived relaxing factor(s) in canine blood vessels.

The effects of phorbol esters on endothelium-dependent relaxations evoked by ACh and the calcium ionophore A23187 were analyzed in isolated canine femoral and coronary arteries mounted in organ chambers or in a bioassay system. In rings of femoral and coronary arteries, phorbol 12,13-dibutyrate (PDBu) (10(-7) M) evoked contraction (ED50 2.9 x 10(-8) M) and depressed endothelium-dependent relaxations to ACh (4-fold increase in ED50 and 72% depression of maximal response). PDBu depressed maximal relaxations to A23187 by 50% but had no effect on ED50. The inactive phorbol ester 4-alpha-phorbol didecanoate (10(-7) M) did not evoke contractions and had no effect on endothelium-dependent relaxations to ACh or A23187. Endothelium-independent relaxations to sodium nitroprusside were not effected by PDBu (10(-7) M) in femoral or coronary arteries. In bioassay experiments, selective treatment of perfused femoral artery segments with PDBu (10(-8)-10(-6) M) caused concentration-dependent inhibition of basal and ACh- (10(-6) M) and A23187-(10(-6) M) induced release of endothelium-derived relaxing factor (EDRF) (as assessed by relaxation of superfused bioassay coronary artery rings without endothelium). PDBu inhibited these responses with different potency: basal (10(-8) M) greater than ACh (10(-7) M) much greater than A23187 (only partial inhibition at 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

Role of calcium in the activation of endothelial cells.

The involvement of calcium in the release of EDRF from cultured endothelial cells is reviewed. It is suggested that both intracellular and extracellular calcium can release EDRF depending not only on the experimental conditions but also on the agonist involved in the release. Calcium enters the cell, following receptor occupation, through a nonselective receptor-operated channel. Intracellular release of calcium following receptor occupation is probably via the production of inositol trisphosphate (IP3). It is suggested that the initial calcium signal for the release of endothelium-derived relaxant factor (EDRF) is of intracellular origin whereas the maintained release of EDRF is due to calcium entry from the extracellular space.

Animals↗
PubMed1987

Calcium regulation in vascular smooth muscle contractility.

The contractile activity of vascular smooth muscle is regulated by control over the cytoplasmic calcium concentration. The intracellular calcium receptor is calmodulin, which, through stimulation of myosin light chain kinase, can activate 2 different contractile states. The calcium is supplied from the sarcoplasmic reticulum and the extracellular space; a minor component is supplied from the inner surface of the plasmalemma. The main intracellular messenger responsible for the transduction of receptor occupation and calcium release from the sarcoplasmic reticulum is IP3 and, to a lesser extent, calcium itself. The superficial location of the sarcoplasmic reticulum in vascular smooth muscle makes it the logical area for control of calcium entry due to calcium leak or through either or both types of calcium channel. The sarcoplasmic reticulum, therefore, acts as a "superficial calcium buffer barrier" and is probably the major system controlling free cytoplasmic calcium concentration in vascular smooth muscle.

Animals↗
PubMed1987

Calcium entry through receptor-operated channels in bovine pulmonary artery endothelial cells.

The activation of endothelial cells by endothelium-dependent vasodilators has been investigated using bioassay, patch clamp and 45Ca flux methods. Cultured pulmonary artery endothelial cells have been demonstrated to release EDRF in response to thrombin, bradykinin, ATP and the calcium ionophore A23187. The resting membrane potential of the endothelial cells was -56 mV and the cells were depolarized by increasing extracellular K+ or by the addition of (0.1-1.0 mM)Ba2+ to the bathing solution. The electrophysiological properties of the cultured endothelial cells suggest that the membrane potential is maintained by an inward rectifying K+ channel with a mean single channel conductance of 35.6 pS. The absence of a depolarization-activated inward current and the reduction of 45Ca influx with high K+ solution suggests that there are no functional voltage-dependent calcium or sodium channels. Thrombin and bradykinin were shown to evoke not only an inward current (carried by Na+ and Ca2+) but also an increase in 45Ca influx suggesting that the increase in intracellular calcium necessary for EDRF release is mediated by an opening of a receptor operated channel. High doses of thrombin and bradykinin induced intracellular calcium release, however, at low doses of thrombin no intracellular calcium release was observed. We propose that the increased cytosolic calcium concentration in endothelial cells induced by endothelium dependent vasodilators is due to the influx of Ca2+ through a receptor operated ion channel and to a lesser degree to intracellular release of calcium from a yet undefined intracellular store.

Animals↗
PubMed1987

Modulation of vascular smooth muscle sensitivity by preload and eicosanoid synthesis inhibition.

An increase in preload from 0.75 to 10 g caused an increase in the sensitivity of rabbit aortic strips to phenylephrine, serotonin, and KCl. Several eicosanoid synthesis inhibitors were utilized to determine whether production of endogenous eicosanoids contributed to the change in muscle sensitivity. Quinacrine (10 microM), indomethacin (10 and 50 micrograms/ml), meclofenamate (50 and 100 micrograms/ml), 5,8,11,14-eicosatetraynoic acid (ETA, 50 and 100 micrograms/ml), and nordihydroguaiaretic acid (NDGA, 10 microM) all shifted the concentration-response curves of various agonists to the right, indicating a decrease in the sensitivity of the muscle to these agents. Thromboxane synthesis inhibition by 1 microM (E)-3-[4-(1-imidazolylmethyl]phenyl-2-propenoate (OKY 046) exerted no effect on sensitivity. Indomethacin at both concentrations caused a parallel shift in the high and low preloaded strips but was unable to alter the influence of preload on sensitivity. A similar effect was observed with the lower concentrations of meclofenamate and ETA. NDGA and higher concentrations of meclofenamate and ETA not only shifted the sensitivity in both high and low preloaded strips but also eliminated the preload effect. These results indicate that cyclooxygenase and lipoxygenase metabolites both alter aortic smooth muscle sensitivity to contractile agents and suggest that lipoxygenase metabolites may play a role in the change in sensitivity seen with preload.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1986

Opiate withdrawal: inpatient versus outpatient programmes and preferred versus random assignment to treatment.

The relative effectiveness of an inpatient and an outpatient withdrawal programme for opiate addicts was studied. Forty five men and 15 women (mean age 26.13 (SD 5.12) years) took part in the study, all of whom were voluntary patients at the drug dependence clinic of the Maudsley Hospital in London between 1984 and 1985. Subjects were asked if they were prepared to accept either inpatient or outpatient withdrawal, and those who were willing to do so were assigned randomly to the randomised outpatient group or the randomised inpatient group. Those who expressed a strong preference were assigned, as appropriate, to the preferred outpatient group or the preferred inpatient group. Addicts in the inpatient group were more likely to achieve complete withdrawal (25 out of 31, 81%) than those in the outpatient group (five out of 29, 17%). This difference could not be attributed to pretreatment factors related to drugs or to social or psychological differences between the groups. These results have clinical and policy implications for the treatment of opiate addicts.

Adult↗
PubMed1986

Ca2+ regulation of vascular smooth muscle.

Regulation of intracellular free Ca2+ concentrations in vascular smooth muscle is accomplished mainly by Ca2+ channels and ATP-dependent Ca2+ pumps in the plasmalemma and sarcoplasmic reticulum (SR). Ca2+ entry through the plasmalemma is apparently mediated by four different pathways: leak; receptor-operated Ca2+ channels; potential sensitive Ca2+ channels; and stretch-activated channels. The agonist releasable intracellular Ca2+ store appears to be identical with the SR. Evidence for the involvement of Ca2+-induced Ca2+ release and inositol-1,4,5-trisphosphate in the release of SR Ca2+ is discussed. Smooth muscle contractions induced by certain agonists may be further enhanced by inhibition of Ca2+ uptake by the SR and of active Ca2+ extrusion across the plasmalemma. At the moment it is not clear from a consideration of the Ca2+ regulatory mechanisms present in vascular smooth muscle how dietary Ca2+ affects vascular tone. The increased Ca2+ permeation through smooth muscle cell membranes of resistance arteries taken from spontaneously hypertensive rats may be relevant to this problem.

Animals↗
PubMed1986

Relationship of endogenous magnesium and calcium levels to oxytocin augmentation.

The relationship between plasma levels of magnesium (Mg) and calcium (Ca) and the plasma Ca to Mg ratios has been investigated in two groups of women. One group of 19 women required augmentation of labor with oxytocin and the control group of 50 patients had normal successful labor. The Mg levels in the plasma were significantly higher in those patients requiring oxytocin augmentation of labor and the Ca/Mg ratio was significantly lower. In the control group, 13 out of the 50 patients had Ca/Mg ratios below 3, whereas 13 out of 19 patients requiring augmentation of labor with oxytocin had Ca/Mg ratios below 3.

Calcium↗
PubMed1985

The effects of prostacyclin (PGI2) on haematological and haemodynamic parameters, and lung histology in puppies undergoing cardiopulmonary bypass surgery with profound hypothermia.

Puppies 6-12 kg underwent cardiopulmonary bypass with profound hypothermia. Thirteen animals received 200 ng kg-1 min-1 of PGI2 during bypass whilst 11 control animals received equivalent volumes of glycine buffer (placebo) over a similar period. Results indicated preservation of platelets, leukocytes and fibrinogen levels, together with shortened activated partial thromboplastin times and fewer fibrinogen degradation products post-bypass in PGI2-treated animals. There was an initial fall in blood pressure and systemic vascular resistance in PGI2 treated animals, but pulmonary pressures and resistances, cardiac outputs, and heart rates showed no significant differences from controls. Higher and more satisfactory end of bypass and post-bypass blood pressure levels, together with a lesser fall-off in mean total pulmonary compliance, and shortened bypass times were achieved in treated animals. PGI2 appeared to afford some protection against lung damage as observed by histological studies. All beneficial effects appeared to be significantly greater amongst smaller animals. The results indicate possible benefits from the use of PGI2 in infant open heart surgery.

Animals↗
PubMed1984

Altered hypothalamic monoamine metabolism and pituitary prolactin regulation in female spontaneously hypertensive rats.

Prolactin (PRL) secretion after aromatic amino acid decarboxylase inhibition with NSD-1015 was significantly elevated in female spontaneously hypertensive rats (SHR) as compared to normotensive (WKY) controls. Although basal PRL levels tended to be elevated in SHR rats, the differences were not significant. In vitro PRL secretion was also significantly elevated in the SHR rats as compared to the WKY rats, but the SHR rats were more responsive to the inhibitory effects of dopamine (DA). Despite changes in pituitary PRL secretion and DA response, there was no apparent difference in tubero-infundibular DA activity between the two rat strains. Hypothalamic serotonin levels were elevated in SHR rats, but metabolism did not appear to be significantly changed based on measurements of 5-hydroxytryptophan accumulation after NSD-1015 treatment.

Animals↗